1. Field of the Invention
The field of the present invention is that of aerosol compositions and more particularly those consisting of propelled film-forming substances which are useful especially, but not exclusively, for the application of a curative protective film to lesions, for example skin lesions.
More precisely, the present invention relates to an aerosol composition for forming a preferably hydrated membrane.
The invention further relates to the preferably hydrated membrane obtained from the abovementioned aerosol composition.
Without implying a limitation, the invention relates more specifically to the application of this aerosol composition and this preferably hydrated membrane for the dressing of wounds, burns or the like.
2. Description of the Prior Art
The purpose of dressing these local traumatisms, often on the skin, is to protect them from the external environment so as to avoid bacterial contamination and allow rapid healing of high quality. To this end, the dressing should obviously be biocompatible so as to be perfectly tolerated, and should preferably be transparent so that the condition and progress of the traumatism can be checked easily.
It is also advantageous for the dressing to possess a degree of mechanical strength, to be permeable to water vapor and also to be easy and painless to apply and remove.
The most traditional dressing is the one consisting of gauze (optionally mounted on adhesive plastic tape). The major disadvantage of this type of dressing is that it adheres too strongly to the wound, whereby the changes of dressing, which are of necessity relatively frequent, are delicate and painful operations. Moreover, the dressed lesions are in most cases suppurant, causing obstruction of the gauze or similar dressing. The dressing consequently becomes impermeable, thereby detracting from the healing and curing of the lesion.
Propelled film-forming substances for dressings are also known which consist of aerosol compositions comprising an active polymer as the film-forming substance, said polymer being capable of forming, after vaporization, a biocompatible film which adheres conveniently to the skin and is transparent and elastic, to name only some of the abovementioned properties expected for application as a dressing.
A wide variety of aerosol compositions containing a film-forming polymer have already been proposed. The following examples may be mentioned:
a composition containing polyvinyl acetate, polyvinylpyrrolidone and acetic acid (cf. FR-A-1 589 917), PA1 a composition based on curable polysiloxane, of the two-component type, associated with a propellant gas (cf. FR-A-2 589 737), PA1 a composition consisting of polyacrylates or methacrylates, ethyl cellulose, polyvinylbutyral, an ethylene oxide copolymer or a polyisobutylene in solution in solvent such as butanol (cf. FR-A-2 219 793 and FR-A-2 212 134), PA1 or else a composition containing an ammonium salt of organosilicon compounds bonded to organic polymers such as polyvinylpyrrolidone or cellulose acrylate or methacrylate, associated with a solvent propellant (cf. U.S. Pat. No. 4,921,691). PA1 cohesion, PA1 permeability to water vapor and oxygen, PA1 impermeability to bacteria, PA1 biocompatibility, tolerance and non-toxicity, PA1 healing promoter, PA1 analgesic, PA1 convenient adhesion to the damaged area, while remaining detachable with ease and without pain, and PA1 preferably a hydrated state which provides a degree of flexibility and a degree of elasticity and which accelerates the curing process (M. F. JONKMAN in "High Performance Biomaterials", Ed. M. Szycher, Technomic (1991)). PA1 a low unit treatment cost because-of the small amount of product required per dressing, and substantial ease of use, which would make the product suitable for use by the general public, and PA1 variety and flexibility as regards the size of the dressings (surface area and thickness). PA1 to render compatible a mixture of a hydrophobic phase containing a film-forming polymer, and a hydrophilic phase, so as to prevent precipitation of the polymer and allow simultaneous vaporization of these two phases to give a membrane, PA1 to give this membrane good cohesion, and PA1 preferably, to ensure that this membrane is suitably hydrated. PA1 at least one hydrophobic phase containing a hydrophobic polyamino acid which is at least partially solubilized in an organic solvent system and is preferably selected from polyamino acids obtained from at least one of the following hydrophobic amino acids or derivatives: alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan and aspartic and glutamic acid esters, PA1 at least one, preferably aqueous, hydrophilic phase, and PA1 at least one propellant. PA1 1--how to vaporize both the hydrophobic and hydrophilic phases simultaneously, PA1 2--how to obtain a cohesive film rather than a mass of individual particles, and PA1 3--how the polymer could trap the water after vaporization and evaporation of the solvent. PA1 chlorofluorocarbons and analogs, PA1 hydrogenofluorocarbons and analogs, PA1 chlorocarbons and analogs, PA1 acetals, PA1 ethers, PA1 esters, PA1 ketones, PA1 alcohols, and PA1 mixtures thereof, PA1 from 0.1 to 10%, preferably from 0.5 to 5%, in the case of lower alcohols, and PA1 from 0 to 50%, preferably 5 to 10%, in the case of polymeric alcohols. PA1 the hydrophobic organic phase of the composition comprises PA1 while its hydrophilic phase contains water, and PA1 a polyol, preferably a polyethylene glycol,
The constituent polymers of these known aerosol compositions have the disadvantage of producing non-hydrated films which are not entirely satisfactory in terms of healing. Moreover, it is clear that, in all probability, these polymers comprise unnatural residual monomers which are capable of generating inflammatory reactions on account of their toxicity towards a living medium (e.g. acrylic derivatives and siloxanes).
In an attempt to improve these vaporizable aerosol compositions for dressings, EP-A-0 521 455 has proposed replacing the known, imperfect film-forming polymers with a biodegradable hydroxycarboxylic acid polymer. The polymer in question can be a polylactic and/or polyglycolic polymer dissolved in a propellant solvent such as dimethyl ether, a freon, a gaseous alkane (e.g. liquefied propane) or an analog of said solvents. This aerosol composition also comprises water and an alcohol such as ethanol, which is useful as a solvent for various therapeutic active principles which may be present.
Despite the advantages of their biocompatibility and biodegradability, these hydroxycarboxylic acid polymers suffer from a serious shortcoming associated with the quality of the film they can produce after vaporization. In fact, it is found that the aerosol compositions based on these hydroxycarboxylic acid polymers are the center of a macroscopic phase separation during vaporization, the consequence of which is to eliminate the water to give a dry film. Such a product seems to be rather unsuitable for the dressing of wounds, burns or the like because its excessively anhydrous nature means that it either has difficulty adhering to the wound or adheres to it too strongly, which causes difficulties and pain when the film is detached.
There is therefore an obvious need for an aerosol composition based on a biocompatible, biodegradable and non-toxic polymer and pharmaceutically acceptable excipients which, on vaporization, can produce inter alia dressings in the form of films, the latter meeting specifications appropriate to this application:
A solid form of dressing or temporary skin substitute is known which has all these properties; it is in the form of a flexible, translucent, colorless membrane marketed under the name INERPAN.RTM.. This skin substitute consists of a leucine/methyl glutamate copolymer impregnated with a liquid based on polyethylene glycol, sodium chloride and purified water.
Although INERPAN.RTM. has demonstrated perfectly its efficacy for the dressing of burns and bedsores in particular, it only exists in the form of thick membranes of predetermined dimensions. Moreover, the application of this dressing requires cautious manipulation and use, limiting its use in today's hospital environment.
It follows from the above that the development of a polymer formulation based on amino acids which formed a film on vaporization would be a totally desirable and valuable technical development, particularly in the field of human health and especially with a view to application as a dressing.
The spray form of a biocompatible, preferably hydrated membrane would represent a novel product, both in design and in realization, and would have the following advantages over the presently known, conventional, non-vaporizable dressings based on hydrogel membranes:
Consequently, one of the essential objectives of the invention is to provide a pharmaceutically acceptable aerosol composition for forming a hydrated membrane after vaporization, said membrane being usable especially as a dressing and possessing the properties referred to above, particularly those of a cohesive, preferably hydrated, biocompatible and therapeutically effective film. To achieve this and other objectives, the Applicant succeeded, after numerous experiments and studies, in solving the problem of which some of the aspects are as follows: